Monday, 12 January 2015

Vitamin D and MS disease course

Chicken or egg; does MS lower vD levels or does low vD levels make MS worse? #MSBlog #MSResearch

"Chicken or egg; what came first? The following study demonstrates that MSers with progressive disease have lower vD levels than RRMSers. Why? Could it be that progressive MSers have less sun exposure, or different diets, as a result of their disability? Until we do an adequately controlled trials we won't know if vD deficiency is caused by active MS, or vD deficiency drives MS disease activity and makes MS worse. Is vD the causative agent, or is reverse causation more likely? The latter refers to the consumptive vitaminopathy hypothesis; i.e. the more active your immune system is the more it consumes vD and lower your blood levels of vD. If the latter is the case giving vD supplements to MSers will have no effect on MS disease course. Why then do we recommend vD supplements to our patients? We do this for bone health and not MS."

"There are several ongoing trials of vD supplementation in MS. I am not sure if these trials will give us a definitive answers regarding vD being disease-modifying; based on my own calculations these trials are underpowered to give a definitive answer. Finally, it vD may not be what is important but actual sunlight exposure; low vD levels are a marker of a lack of sunlight exposure. There is immunological data suggesting that exposure of lymphocytes to UV-light in the skin is immunomodulatory and the low vD levels are simply an association. What is clear is that there are many questions that need answering in relation to vD and MS. It is a great pity that the community has not be able to get the needed funding to do the definitive experiment."

"You may find my previous presentation on this topic helpful."


Epub: Thouvenot et al. Vitamin D is associated with degree of disability in patients with fully ambulatory relapsing-remitting multiple sclerosis.Eur J Neurol. 2014 Dec 20. doi: 10.1111/ene.12617.

BACKGROUND AND PURPOSE: Vitamin D deficiency is a recognized risk factor for multiple sclerosis (MS) and is associated with increased disease activity. It has also been proposed that the lower the vitamin D levels are, the higher is the handicap.

METHODS: To refine the links between vitamin D insufficiency and disability in MSers, a retrospective cohort analysis was performed including 181 MSers prospectively followed without previous vitamin D supplementation, and age, gender, age at MS onset, MS type, MS activity, Expanded Disability Status Scale (EDSS) were analysed in correlation with plasma vitamin D levels.

RESULTS: Vitamin D levels were significantly higher in relapsing-remitting MS than in progressive forms of MS in multivariate analyses adjusted for age, ethnicity, gender, disease duration and season (P = 0.0487). Overall, there was a negative correlation between vitamin D level and EDSS score (P = 0.0001, r = -0.33). In relapsing-remitting MS, vitamin D levels were only correlated with disability scores for EDSS < 4 (P = 0.0012). MSers with >20 ng/ml of vitamin D were 2.78 times more likely to have an EDSS < 4 (P = 0.0011, 95% confidence interval 1.49-5.00).

CONCLUSION: Data support previous work suggesting that vitamin D deficiency is associated with higher risk of disability in MS. Vitamin D levels also correlated with the degree of disability in fully ambulatory patients with relapsing-remitting MS. These additional results support the pertinence of randomized controlled trials analysing the interest of an early vitamin D supplementation in MS patients to influence evolution of disability.

24 comments:

  1. Your conclusion Prof G is spot on!

    It's the sun which is protective not just VitD. I realise that each summer when I sunbathe cos my symptoms go away much quicker.

    I got MS in a period of time when I had not been in the sun literally for years cos I was stucked in an office until late afternoon!

    My Mum on the other hand never got anything when younger cos she was a sunbathing fanatic (except when pregnant with me!! due to pregnancy difficulties) but later on she got autoimmune gastritis and HER VitD are as low as mine now.

    So it's the sun and low VitD levels are not exclusively related to MS but other autoimmune diseases as well and maybe even cancers.

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  2. May be there is also something else we get from sunlight. Is there much research into seasonal changes and disease including MS?
    From my limited understanding of physiology, seasonal changes on the pineal gland, has shown that animals are very sensitive seasonal changes. As the days become longer and the amount of light stimulation increases.
    This then has effect on meletonin secreted, which regulates other vital glands especially ones involved in reproduction. If we look at SAD seasonal effectiveness disorder which brings on depression. In Northern countries SAD occurs, caused by lack of sunlight. which influences activity on the pineal gland.

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  3. How about this:
    Genetic evidence for a pathogenic role for the vitamin D3 metabolizing enzyme CYP24A1 in multiple sclerosis.
    Ramasamy A, Trabzuni D, Forabosco P, Smith C, Walker R, Dillman A, Sveinbjornsdottir S; North American Brain Expression Consortium (NABEC), UK Brain Expression Consortium (UKBEC), Hardy J, Weale ME, Ryten M.
    Mult Scler Relat Disord. 2014 Mar;3(2):211-219.

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  4. In Brazil and Portugal there are thousands of people curing autoimmunity with high dose vitamin D

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    1. Perhaps speaking Portuguese is the cure for autoimmunity? ;-)

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    2. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897595/

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  5. Clearly the rest of the MS scientific community has uncovered facts that vitamin D levels are associated with a better outcome for RRMS.

    http://www.ncbi.nlm.nih.gov/pubmed/22926855

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    1. Re: "Clearly the rest of the MS scientific community has uncovered facts that vitamin D levels are associated with a better outcome for RRMS."

      We agree with them and you; the importance is use of the word association and not causation. Association could also mean reverse causation, i.e. the less active your MS the less active your immune system the less vD consumption by the immune cells the higher peripheral vD levels. The only way to get an answer is with a clinical trial (experiment).

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  6. Mousedoctor or Prof G

    What dose would you consider the limit for Vit D supplementation in pregnant women?

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    1. Re: "What dose would you consider the limit for Vit D supplementation in pregnant women?"

      We refer people to the vD council: https://www.vitamindcouncil.org/further-topics/vitamin-d-during-pregnancy-and-breastfeeding/

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    2. If you scale up the recommendation by the Royal College of Paediatrics and Child Health for new born babies (400iu a day, average weight 3.4kg) using mass as an approximation for volume, you get a dose for an largish adult of about 12,000IU a day (100kg). Somewhat higher than the current RDA for an adult. There are no know cases of toxicity at 10,000IU a day.

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    3. Re: "you get a dose for an largish adult of about 12,000IU"

      In an ideal world you would treat to target to maintain a blood level above 100nmol/L or 40ng/mL, but less than 250nmol/L or 100ng/mL. The vD council goes for 5,000 U/day to target the population; this is too much for some and too little for others.

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  7. "The latter refers to the consumptive vitaminopathy hypothesis; i.e. the more active your immune system is the more it consumes vD and lower your blood levels of vD." " If a more active immune system consumes more vitamin d, then it is fair to say it is doing something with it. What exactly is it doing with it? And why would you not want to supply the body with more? I thought that low 25(OH)D increased active immune system activity and inflammation, is this correct?

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    1. Re: "I thought that low 25(OH)D increased active immune system activity and inflammation, is this correct?"

      It may be the other way around; immune activity consumes extra vD. The public health doctors call this reverse causation.

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    2. If "immune activity consumes vitamin d" would you not want to replace the vitamin d so the person is not deficient? So no matter which way round the causation is, more vitamin d is needed. It may not stop MS but it might stop bone loss.


      You may be interested in: Front Physiol. 2014; 5: 151.
      Published online Apr 21, 2014. doi: 10.3389/ fphys.2014.00151 PMCID: PMC4000998

      Impact of vitamin D on immune function: lessons learned from genome-wide analysis
      Rene F. Chun Philip T. Liu Robert L. Modlin John S. Adams and Martin Hewison

      The statement under perspectives "A key challenge going forward will be to relate these mechanisms to patient vitamin D status, and this is likely to herald a new wave of genome-wide analyses linked to placebo-controlled vitamin D supplementation trials. Interpretation of these studies is likely to be complex. Recent genome-wide analysis of patient tissues has shown that some immune diseases are characterized by corruption of the vitamin D system, so that conventional notions of vitamin D-sufficiency and vitamin D-deficiency may be very different for patients with specific diseases."

      If this is true getting the trial design correct is going to be fun.


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  8. My vit D blood levels have changed. I was at low vit D when first diagnosed. Then I was first taking just 400 iu daily for 12 months. Then 2,000 iu daily for 8 months. Then 4, 000 iu daily for the last 8 weeks. Blood tests results back today ( blood taken 8 weeks ago), i've been eating oily fish 2 or 3 times a week too. Vit D level is now 97 (informed normal is between 50-120). I was quite surprised by the change. I have smouldering RRMS.

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  9. To help further discussion of vitamin d it is useful to have seen this paper, which seems to have received very little publicity, It shows how the RDA recommended by the IOM in the USA was badly miscalculated.

    Keep it in mind when people say 5000IU a day is much too high.

    Veugelers PJ, Ekwaru JP. A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Nutrients 2014;6(10):4472-4475. doi:10.3390/nu6104472.

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    Replies
    1. Please could you post a link to the actual article (if anything more than just the abstract is available)

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  10. The actual link is http://www.mdpi.com/2072-6643/6/10/4472/htm but I don't know if that will show up when I post this.

    It is a letter article in the Journal "Nutrients". It is free to read. the doi will find it. paste doi:10.3390/nu6104472 into Google, second one down is www,mdpi,com that's the publisher it should go straight to the article.

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    Replies
    1. Thank you - the link works if you copy it as text from this webpage and paste it into the address field on your browser

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  11. am loving this, all these doc's need to go back in time and read what I read some where stress same thing as vt d not going to where it's sopost to in the brain ,ok it was done in monkey brains not mice in study's 30-40 years ago

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  12. Dr. Giovannoni:
    ¿Have sense vD with Protandim for MS? ¿What do you think? http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=137548&XNSPRACHE_ID=2&XNKONGRESS_ID=150&XNMASKEN_ID=900

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  13. This just announced. Essentially in the UK there's not enough sunlight to maintain a high enough level of vitamin D. Supplementation recommended.
    http://www.theguardian.com/lifeandstyle/2015/aug/02/britain-not-sunny-enough-healthy-vitamin-d-levels-supplements

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    1. What a surprise! Shame they are not producing the final report until next year and say people should stick with current vitamin D government recommendations until then!

      I've been taking D3 5000iu for over 20 years, and try to get as much sunlight as possible, eat lots of scrambled eggs etc. And have my levels tested twice a year and just scrape into the optimum zone (Vitamin D Council one, by UK standards I'm well over).

      So I wonder how low the average UK levels are for people who don't take a D3 supplement?

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